It is well acknowledged that proinflammatory stimulation during acute hyperglycemia is able to aggravate inflammatory diseases. However, the mechanisms of proinflammatory effects of glucose are controversially discussed. We investigated leukocyte recruitment after intravenous injection of glucose in different inflammatory models using intravital microscopy. Flow chamber experiments, expression analysis, functional depletion, and knockout of key adhesion molecules gave mechanistic insight in involved pathways. We demonstrated that a single injection of glucose rapidly increased blood glucose levels in a dose-dependent manner. Notably, during tumor necrosis factor (TNF) α-induced inflammation leukocyte recruitment was not further enhanced by glucose administration, whereas glucose injection profoundly augmented leukocyte adhesion and transmigration into inflamed tissue in the trauma model, indicating that proinflammatory properties of glucose are stimulus dependent. Experiments with functional or genetic inhibition of the chemokine receptor CXCR2, intercellular adhesion molecule 1 (ICAM1), and lymphocyte function antigen 1 (LFA1) suggest that keratino-derived-chemokine CXCL1-triggered interactions of ICAM1 and LFA1 are crucially involved in the trauma model of inflammation. The lacking effect of glucose on β2 integrin expression and on leukocyte adhesion in dynamic flow chamber experiments argues against leukocyte-driven underlying mechanisms and favours an endothelial pathway since endothelial ICAM1 expression was significantly upregulated in response to glucose. 1. Introduction Although proinflammatory effects of acute hyperglycemia in inflammatory conditions and septic patients have been extensively investigated in clinical as well as experimental settings, there are still controversies about its relevance and mechanisms [1, 2]. In contrast to earlier studies Brunkhorst et al. found no beneficial effect of treating acute hyperglycemia in the clinical setting of sepsis [3]. However, in this context it was difficult to dissect between effects directly attributable to insulin or thereby induced hypoglycemia. Similarly, hyperglycemia-related proinflammatory effects should be separated into those directly evoked by glucose and those induced by secondary hyperglycemia (stress, inflammation). In case of acute hyperglycemia caused by critical illness, altered secretion of counterregulatory hormones and excessive release of proinflammatory cytokines is observed as well as suppression of the innate immune system [4, 5]. These consequences of impaired leukocyte
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